Determination of the success of treatment of primary biliary cirrhosis (PBC) with ursodeoxycholic acid (UDCA) and methotrexate (MTX). PBC is a disease of unknown cause in which the small bile ducts in the liver are destroyed slowly by inflammation. It is believed that this can be due to an abnormal immune response directed against the bile ducts. PBC is considered to be an autoimmune disease. Loss of bile ducts causes bile to back up into the liver and ultimately leads to liver damage, liver cirrhosis, and possibly liver failure and death. Recent information suggests that the combination of UDCA and MTX may be useful in the treatment of PBC. This study is designed to examine whether treatment with the two medications is better than treatment with one, and it will be a comparison to treatment with UDCA and a placebo. The study will last for ten years. The treatment study will consist of two phases. In phase I, the UDCA phase, patients will take UDCA for at least six months. In phase II, the MTX/placebo phase, patients will be randomized to receive MTX or its placebo while continuing to receive UDCA. Patients will continue on long term combined therapy for at least five years if there is no evidence of drug toxicity. Subjects must have documented PBC. They will be assigned to add MTX or a substance that looks like MTX but is a placebo.The UDCA will be continued to be used. Complete examinations and blood, bile, and urine tests will be performed at the entry and at intervals throughout the study. Upper endoscopy and liver biopsy will be required prior to entry and at two to two and a half year intervals.